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Correction published on 24 December 2025, see Curr. Issues Mol. Biol. 2026, 48(1), 17.
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Article

Anti-Inflammatory Effect of Pineapple Rhizome Bromelain through Downregulation of the NF-κB- and MAPKs-Signaling Pathways in Lipopolysaccharide (LPS)-Stimulated RAW264.7 Cells

by
Orapin Insuan
1,2,
Phornphimon Janchai
3,
Benchaluk Thongchuai
1,2,
Rujirek Chaiwongsa
4,
Supaporn Khamchun
1,2,
Somphot Saoin
1,2,
Wimonrut Insuan
5,
Peraphan Pothacharoen
6,7,
Waraporn Apiwatanapiwat
3,
Antika Boondaeng
3 and
Pilanee Vaithanomsat
3,8,*
1
Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand
2
Unit of Excellence in Integrative Molecular Biomedicine, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand
3
Nanotechnology and Biotechnology Research Division, Kasetsart Agricultural and Agro-Industrial Product Improvement Institute (KAPI), Kasetsart University, Bangkok 10900, Thailand
4
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
5
Department of Veterinary Technology, Faculty of Veterinary Technology, Kasetsart University, Bangkok 10900, Thailand
6
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
7
Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
8
Center for Advanced Studies in Tropical Natural Resources, National Research University-Kasetsart University, Kasetsart University, Bangkok 10900, Thailand
*
Author to whom correspondence should be addressed.
Curr. Issues Mol. Biol. 2021, 43(1), 93-106; https://doi.org/10.3390/cimb43010008
Submission received: 26 March 2021 / Revised: 4 May 2021 / Accepted: 5 May 2021 / Published: 7 May 2021 / Corrected: 24 December 2025
(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era)

Abstract

Bromelain is a mixture of proteolytic enzymes derived from pineapple (Ananas comosus) fruit and stem possessing several beneficial properties, particularly anti-inflammatory activity. However, the molecular mechanisms underlying the anti-inflammatory effects of bromelain are unclear. This study investigated the anti-inflammatory effects and inhibitory molecular mechanisms of crude and purified rhizome bromelains on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. RAW264.7 cells were pre-treated with various concentrations of crude bromelain (CB) or purified bromelain (PB), and then treated with LPS. The production levels of pro-inflammatory cytokines and mediators, including nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)- were determined by Griess and ELISA assays. The expressions of inducible nitric oxide synthetase (iNOS), cyclooxygenase (COX)-2, nuclear factor kappa B (NF-B), and mitogen-activated protein kinases (MAPKs)-signaling pathway-related proteins were examined by western blot analysis. The pre-treatment of bromelain dose-dependently reduced LPS-induced pro-inflammatory cytokines and mediators, which correlated with downregulation of iNOS and COX-2 expressions. The inhibitory potency of PB was stronger than that of CB. PB also suppressed phosphorylated NF-B (p65), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha, extracellular signal-regulated kinases, c-Jun amino-terminal kinases, and p38 proteins in LPS-treated cells. PB then exhibited potent anti-inflammatory effects on LPS-induced inflammatory responses in RAW264.7 cells by inhibiting the NF-B and MAPKs-signaling pathways.
Keywords: bromelain; inflammation; pro-inflammatory cytokines; NF-B; MAPKs bromelain; inflammation; pro-inflammatory cytokines; NF-B; MAPKs
Graphical Abstract

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MDPI and ACS Style

Insuan, O.; Janchai, P.; Thongchuai, B.; Chaiwongsa, R.; Khamchun, S.; Saoin, S.; Insuan, W.; Pothacharoen, P.; Apiwatanapiwat, W.; Boondaeng, A.; et al. Anti-Inflammatory Effect of Pineapple Rhizome Bromelain through Downregulation of the NF-κB- and MAPKs-Signaling Pathways in Lipopolysaccharide (LPS)-Stimulated RAW264.7 Cells. Curr. Issues Mol. Biol. 2021, 43, 93-106. https://doi.org/10.3390/cimb43010008

AMA Style

Insuan O, Janchai P, Thongchuai B, Chaiwongsa R, Khamchun S, Saoin S, Insuan W, Pothacharoen P, Apiwatanapiwat W, Boondaeng A, et al. Anti-Inflammatory Effect of Pineapple Rhizome Bromelain through Downregulation of the NF-κB- and MAPKs-Signaling Pathways in Lipopolysaccharide (LPS)-Stimulated RAW264.7 Cells. Current Issues in Molecular Biology. 2021; 43(1):93-106. https://doi.org/10.3390/cimb43010008

Chicago/Turabian Style

Insuan, Orapin, Phornphimon Janchai, Benchaluk Thongchuai, Rujirek Chaiwongsa, Supaporn Khamchun, Somphot Saoin, Wimonrut Insuan, Peraphan Pothacharoen, Waraporn Apiwatanapiwat, Antika Boondaeng, and et al. 2021. "Anti-Inflammatory Effect of Pineapple Rhizome Bromelain through Downregulation of the NF-κB- and MAPKs-Signaling Pathways in Lipopolysaccharide (LPS)-Stimulated RAW264.7 Cells" Current Issues in Molecular Biology 43, no. 1: 93-106. https://doi.org/10.3390/cimb43010008

APA Style

Insuan, O., Janchai, P., Thongchuai, B., Chaiwongsa, R., Khamchun, S., Saoin, S., Insuan, W., Pothacharoen, P., Apiwatanapiwat, W., Boondaeng, A., & Vaithanomsat, P. (2021). Anti-Inflammatory Effect of Pineapple Rhizome Bromelain through Downregulation of the NF-κB- and MAPKs-Signaling Pathways in Lipopolysaccharide (LPS)-Stimulated RAW264.7 Cells. Current Issues in Molecular Biology, 43(1), 93-106. https://doi.org/10.3390/cimb43010008

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